Effect of Sorbitol on the Pharmacokinetic Profile of Lamivudine Oral Solution in Adults: An Open-Label, Randomized Study

In children aged <= 4 years, the relative bioavailability of lamivudine oral solution was 37% lower than that of a tablet formulation. An open-label, four-way crossover study was conducted in healthy adults to evaluate the effect of sorbitol, a common liquid excipient, on the pharmacokinetics of lamivudine oral solution (ClinicalTrials. gov identifier, NCT02634073). Sixteen subjects were randomized to one of four sequences consisting of four doses of lamivudine 300mg ( 10 mg/mL) alone or with sorbitol 3.2, 10.2, or 13.4 g. Sorbitol 3.2, 10.2, and 13.4 g decreased lamivudine maximumconcentration (Cmax) by 28%, 52%, and 55% and area under the concentration-time curve fromtime 0 to 24 h (AUC0-24) by 20%, 39%, and 44%, respectively. Three subjects (19%) reported five nonserious adverse events (one drug-related). The dosedependent effects of sorbitol on lamivudine Cmax and AUC0-24 reveal an absorption-based interaction thatmay decrease lamivudine exposure in patients coadministered sorbitol-containingmedicines.